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Amaç: Distrofinopatiler kendilerine özgü ve oldukça geniş klinik ve genetik spektrumu ile nöromusküler hastalıklar içinde halen en sık araştırma konusu olan gruptur. Bu araştırmada bir merkezden elde edilen sonuçlar değerlendirilerek Türkiye’deki distrofin geni delesyon ve duplikasyon profilinin ortaya konulması amaçlanmıştır. Gereç ve Yöntemler: Ankara Şehir Hastanesi Tıbbi Genetik Polikliniği’ne Şubat 2019-Aralık 2020 tarihleri arasında 49’u distrofinopati, 4’ü nörogenetik-sendromik bozukluklar klinik ön tanısı ile yönlendirilen 53 hastaya ait distrofin MLPA ve mikrodizin sonuçları retrospektif olarak değerlendirildi. Bulgular: Çalışmaya alınan 53 hastanın 4’ünde distrofin geninde çeşitli ekzon duplikasyonları saptanmış olup kalan 49 hastada delesyon olduğu görüldü. Bu mutasyonların 33’ü frame-shift (%62.3), 20’si in-frame (%37.7) değişikliğe neden olmaktadır. Maternal çalışma yapılan 50 hasta (%94.3) değerlendirildiğinde 14 hastada (%26.4) de novo mutasyon olduğu görüldü. Distrofin geninde en sık santral rod domain’de (%69.7), ikinci sıklıkla aktin bağlayıcı bölümde (%7.5) mutasyonlar izlenmiştir. Henüz klinik araştırmaları devam eden güncel ekzon atlatma tedavileri açısından çerçeve kayması tipi mutasyona sahip 33 hastanın 12’sinin (%36) aday olduğu saptandı. Sonuç: Bu çalışma ile popülasyonumuz açısından distrofin delesyon/duplikasyon mutasyon sıklıklarına ışık tutulmuş ve henüz rutin kullanıma girmeyen tedaviler açısından dahi hastaların önemli bir kısmının aday olduğu tespit edilmiştir. Son yıllarda gelişen distrofin geni temelli tedavi olanakları da göz önünde tutulursa populasyonlara ait mutasyon tipi sıklıklarının bilinmesi büyük önem taşımaktadır.
Distrofinopaths are a group that is unique to them and has a very broad clinical and genetic spectrum and is the subject of continuous research in neuromuscular diseases. In this study, the results obtained from a center were evaluated and aimed at revealing the distrophin gene division and duplication profile in Turkey. Tools and Methods: From February 2019 to December 2020 to the Ankara City Hospital Medical Genetic Clinic, the results of the 53 patients with distrophin MLPA and microdis were retrospective assessed with a clinical pre-diagnosis of 49 distrophinopathy, 4 neurogenetic-syndromic disorders. Results: Four of the 53 patients surveyed had various exon duplications in the dystrophine gene and the remaining 49 patients had divisions. 33 of these mutations cause frame-shift (62.3%), and 20 in-frame (37.7%). In the maternal study, 50 patients (94.3%) were evaluated and 14 patients (26.4%) had new mutations. In the Distrophine genetic central rod domain (69.7%) mutations were observed in the second most frequently actin binding section (7.5%) Clinical research has found that 12 (36%) of 33 patients with frame swing-type mutation in terms of current exotic transition therapies are candidates. The result: With this study, the frequency of distrophine division/duplication mutation in terms of our population has been highlighted and a significant proportion of patients have been identified as candidates, even in terms of treatments that are not yet in routine use. If the development of the distrophine gene-based treatment possibilities are also taken into account in recent years, it is of great importance to know the frequency of the mutation type of the populations.
Objective: Dystrophinopathies are the most frequently researched neuromuscular disease group due to their characteristic and diverse clinical and genetic spectrum. This study aims to evaluate the deletion and duplication profile of the dystrophin gene in Turkey by investigating data from a tertiary center. Material and Methods: Dystrophin MLPA and microarray results of 53 patients, 49 with a dystrophinopathy and 4 with a neurogenetic and syndromic disorder pre-diagnosis, who were referred to the Medical Genetics Clinic of Ankara City Hospital between February 2019-December 2020 were retrospectively evaluated. Results: Of the 53 patients, 4 had various exon duplications and 49 had deletions. 33 of these mutations caused frame-shift (62.3%), while 20 caused in-frame (37.7%) changes. Fifty (94.3%) patients underwent maternal studies and 14 (26.4%) of these had de novo mutations. Mutations were observed most frequently in the central rod domain (69.7%) followed by the actin-binding domain (7.5%) of the dystrophin gene and 12 of 33 patients with frameshift mutation (36%) patients were found to be candidates for the exon skipping treatments that are still subject to clinical research. Conclusion: This study has shed light on the incidence of dystrophin deletion/duplication mutations in our population and has revealed that a majority of patients are suitable candidates for treatments which are still not in routine use. Considering ever-growing number of dystrophin gene-based treatment options, data on population-specific mutation types is of great importance.
Alan : Sağlık Bilimleri
Dergi Türü : Uluslararası
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